Career Conversations – Jacques Dubochet

I am very much looking forward to the day scientist will be seen as rockstars. People aiming to share their talent to benefit society. Role models. The person we are going to speak about today is surely one of my rockstars. The name of Jacques Dubochet has been in the spotlight since this Swiss biophysicist received the 2017 Nobel Prize in Chemistry, with Joachim Frank and Richard Henderson “for developing cryo-electron microscopy (Cryo-EM) for the high-resolution structure determination of biomolecules in solution”. In other words, these science giants managed to overcome all technical and biological difficulties to develop a technology that captures extremely high-resolution images of biomolecules.

Why is this important? Well, in biology, once you have the structure of a biomolecule (this can be a virus, a protein, or even tinier, a complex of atoms), you can understand its function, for which a whole new world of possibilities opens. For example, when in 2016 the World Health Organization declared the Zika virus epidemic as ‘a public health emergency of international concern’, scientists joined forces to investigate the complex mechanisms by which this virus was producing such devastating symptoms. The Cryo-EM technique helped in the definition of the Zika virus structure, so we could have information on every corner of the virus, how different it was from other viruses of the same family, and possible ways of recognition and neutralization with antibodies. These insights, which managed to provide the Zika virus structure in the 3.8 Å resolution, earned no-least than a Science paper (see reference here).

The three 2017 Nobel prize awardees helped in three different but essential ways to the development of this technique, and in the following interview we will get to know with which piece Jacques Dubochet contributed to this intricate puzzle. I am absolutely fascinated by the way Jacques divulgates his research, in such an approachable, down-to-earth, understandable, exciting, funny and, principally, humble way. See what I am referring to in his 2017 Nobel lecture (watch here, you won’t regret). Voilà. Stefanie Ginster recently talked to Jacques in her Career Conversations, so I will provide the transcription of this conversation – which you can also find here. Stefanie’s questions are in bold, while Jacques answers are written below. I also took the liberty to get intermingled with such a magnificent interview by providing my comments in italic.

Let’s start!

Jacques, could you explain to me what is exactly Cryo – EM?

When you are interested in biology, and you want to observe things in the electron microscope (EM), the ‘thing’ must be dry. This is because the EM must be in vacuum, as electrons cannot pass through air. In the vacuum, water evaporates, but most of the interesting things to see are in water! If you remove water, it’s like a fish in an aquarium without water. We had a project to learn how to deal with water in the electron microscope, and we reached a simple idea…freeze it! Keep the water in the frozen state, and that’s what we did! But then we reached another problem: ice is as damaging to the biological sample as no water. So, we tried to find a solution and then, by chance, we discovered how is possible to cool the water without damaging the sample. This is called vitrification….

Note: so liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse. In the early 1980s, Jacques succeeded in vitrifying water – cooling down water so rapidly that it solidified in its liquid form (without crystallizing) around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

…it was thought to be impossible! This was the origin of Cryo-EM of vitreous samples: having biological matter in the original state with frozen water. And this took 35 years to improve! Learning how to deal with the microscope, managing the mathematical data, working with other people. After 35 years the resolution made possible to see atoms, and when you see atoms, then we change [field] to chemistry. Chemists were really interested in our data. They love 3D atomic structures, and the [Royal] Swedish Academy of Sciences also loved it, so they gave us the Nobel Prize.

When you discovered that water could be vitrified to be used for Cryo-EM, you tried to submit those results to Nature, for which they answered, “You can’t bend Nature”. How did you cope with this?

Nature rejected, but there was the same discovery in press by another group, with another method and with another way of proving it, demonstrating that vitrification was possible. Later, the editor of the journal of microscopy approached me to urge the publication of what we discovered and arranged for us to quickly publish these results. It was a very short one-page note with two small photographs just saying that we knew how to vitrify for microscopy.

So your way to deal with frustration was just to keep going?

Yes.

Maybe most people wouldn’t respond like this, as publishing seems to be the most important thing nowadays.

I noticed that, nowadays, PhD students publish 3-times more than what I was publishing at that time! This is a problem. Slow science is not important anymore and time is very important.

I will make a small pause in the conversation to really emphasize this point. Slow science IS important. When we have deadlines, papers to publish or grants to write, experiments are rushed, and we start doing science for survival (of the best researcher in that particular topic) and less for knowledge. This is something that should change. We should be able to leave our brains wonder, reach new ideas that will lead to innovative experiments. Developing new and adventurous ideas. Actually, further on the conversation, Jacques also made a really good point on being adventurous in research…

See this story: there is a guy looking for a key during the night. Some people come to help him, and an old man asks him ‘Are you sure you lost the key here?’ for which the guy replies ‘No, no! The key is further there, but only here I have light!’ People chose avenues where it is bright, instead of unexplored ones. It does not mean that what is not explored is difficult, just not explored. People should prefer the research which is not the one of all the others! But people make very little effort to try something different.

Why do you think that is?

Our society doesn’t like outliers. See the story of my CV, for instance. When I got the Nobel Prize, journalists discovered my CV, which is a little bit different to others (see what he is refereeing to here). But, why should a CV be boring and uniform? I dream of CVs made as poems, creative CVs. CVs are a reflection of life, and one would say my life is not common, it is different than any other, and I cultivate that.

This would require a lot of reflection on who we really are.

Someway, each of us has some value. Sometimes it is hidden, but people don’t cultivate it. In fact, schools should help people to find their values, something you think “it’s mine, and it’s good”, something you’re proud of. I was very bad at school, but during those times I built a telescope, a quite accurate one. That was “my thing”, and it gave me the strength and confidence to keep going.

What would you say is your most important value?

“Liberté, égalité, fraternité” (wait, wasn’t he Swiss?) Wait, we need to change that. “Fraternité, liberté, égalité”. Voilà. The French revolution, it has its story! (*La Marseillaise starts sounding on the background*). Humans need to be recognized as individuals with rights. It means altruism, helping each other. This century has developed a lot the ‘me’, and less the ‘we’, and we need to reestablish it. CO2 is not ‘me’… CO2, it is ‘ours’! There is urgency to push the ‘we’ and less the ‘I’.

I think that this next part is truly remarkable: what makes a good scientist? Working a lot? Jacques has some words for all of those high achievers…

High achievement. Trying to reach high achievement is not a good goal. Trying to be the best is hopeless! It’s too difficult! Just try to be somebody, for your own. Then see where that leads you. When I was young I wanted to be a high achiever, a great scientist. I was very ambitious. However, later in life I tried to understand myself better. At some point, I had this strange dream where I thought I would be a great scientist, but that was just too difficult. Then, I did my career as a normal scientist. I was a normal PhD and a normal post-doc. The ‘cherry on the cake’ was that I did this surprising discovery…I thought it was a great thing and I run after it.

So when you wanted to be a great scientist, was it because you wanted to be perceived as a great scientist by other people or because you wanted to prove something to yourself?

Certainly both. We are social people, but we also need to be true to ourselves. In my case, I wanted to be recognized, but science was also important. See, when I was young, I was trying to convince my girlfriend that I was a great person to hang out with by explaining Einstein’s theory of relativity…. without any big success.

Not sure if that’s what girls may like!(I disagree with that, explain Einstein’s theory of relativity to me and my heart is yours)

I wanted to be recognized. On the other hand, I hate competition with others, but love competition with myself. During my scientific career, I always chose avenues where I would not come in conflict with others. In my lab, this is a clear statement: we collaborate with each other. Working with collaborative and nice people just makes life better.

Couldn’t agree more! Researchers compete against one another to become specialists in their field, gain a promotion and increase their salaries. Publish or perish. Usually this happens between groups of different institutes researching the same topic, but there can also be competition between members of the same group. There are also fewer job positions, so there is much competition. And don’t get me even started in the case of women, who need to balance professional perspectives, job security and family. How can we do science under these circumstances? I think it’s important to be true to yourself, and as Jacques commented, find your own value. And I would even say, find what you can offer to society, the personal and unique way you could serve for a common good. Only then you will find how you are special.

Next, we will read what Stefanie needs to add on her view of this interview, the anecdotes and curious facts she encountered on the procedure of meeting the Nobel laureate, Jacques Dubochet.

Stefanie: I found the conversation with Jacques truly remarkable. Even though he is a high achiever in science, he has a lot more topics to talk about, so we only exchanged a few sentences about science and then mainly talked about his values and how he approached life in general.

The first thing I noticed about Jacques was that he was perfectly on time, even though as very busy person and would have every reason to be late. This is something that I noticed about most people with outstanding careers. They are very reliable and not even 5 min late. This makes me think that good time management might be one of the biggest keys to success.

When I stepped into Jacques’ office, it turned out that he shares it with a PhD student, which was a huge surprise for me. I expected a Nobel Prize Winner not only to have his own office but also his own parking spot, his own chair in the cafeteria, etc. But, for that matter, Jacques does not even have his own car parking spot but a very humble Nobel Prize bike parking spot. Given that he is so humble today, I was even more surprised when he said that he always wanted to be a “great scientist” and I wondered ever since, whether we should have aims that feel unachievably high at the moment. Obviously it has worked for Jacques but at the same time he says that there is no value in high achievement.

Picture: https://www.reddit.com/r/MadeMeSmile/com.

Finally, I had the impression, that the Noble Prize sometimes is a burden for Jacques. In the end of the interview I asked him, in a nutshell, what general advice he could give to scientists that are struggling with their careers. His response was that he does not want to answer because he feels that I am only asking this question because of his Nobel Prize. First, I was really puzzled because I always end with a more general question that gives the guest the opportunity to sum up what they have said in the interview. It almost seemed like often it is difficult for Jacques to distinguish which questions are sincere or whether the interviewer just wants to stand in the glow of the Nobel Prize and create an inspirational quote from a Nobel Prize winner. So, I see why he thinks that high achievement in and of itself has no value. In the end, being recognized as one of the best in your field does not make people happy. However, one thing that Jacques told his mentee Victoria Baumgartner (who was also a guest on the show), is to always stay ambitious. I guess it just matters what your ambition is. If your ambition is to bring your field forward and to add value to society, then go for it! Collaborate with the best in your field and set your goals high because with lots of brilliant minds together, we can really bring society forward. But if your aim is to just be better than others, then maybe you should find other ways.

His last sentence I like the most in the interview “OK, I continue”. Actually, the context was that he had to leave for his next appointment (once again, punctual!). I love it because my overall impression was that Jacques is not yet done, neither with science nor with life. He could easily take it slow, knowing that he has got the highest award possible in his field but he is still busy working on new projects. So, maybe we should do the same and rather than just focusing on narrow goals, be prepared to never be done and to always continue adding value.